Referenced in: none

Automatically associated channels: Cav3.2

Title: Discovery of N-[[1-[2-(tert-butylcarbamoylamino)ethyl]-4-(hydroxymethyl)-4-piperidyl]methyl]-3,5-dichloro-benzamide as a selective T-type calcium channel (Ca(v)3.2) inhibitor.

Authors: Fabrizio Giordanetto, Andreas Wållberg, Laurent Knerr, Nidhal Selmi, Victoria Ullah, Fredrik Thorstensson, Sa Lindelöf, Staffan Karlsson, Grigorios Nikitidis, Antonio Llinàs, Qing-Dong Wang, Anders Lindqvist, Got Högberg, Emma Lindhardt, Annika Strand, Göran Duker

Journal, date & volume: Bioorg. Med. Chem. Lett., 2013 Jan 1 , 23, 119-24

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23200256

Abstract
The T-type calcium channel inhibitor Mibefradil was reported to protect the heart from atrial remodeling, a key process involved in the development of atrial fibrillation and arrhythmias. Mibefradil is not a selective T-type calcium channel inhibitor and also affects the function of different ion channels. Our aim was to develop a selective T-type calcium channel inhibitor to validate the importance of T-type-related pharmacology in atrial fibrillation. Structural optimisation of a previously disclosed hit series focussed on minimising exposure to the central nervous system and improving pharmacokinetic properties, while maintain adequate potency and selectivity. This resulted in the design of N-[[1-[2-(tert-butylcarbamoylamino)ethyl]-4-(hydroxymethyl)-4-piperidyl]methyl]-3,5-dichloro-benzamide, a novel, selective, peripherally restricted chemical probe to verify the role of T-type calcium channel inhibition on atrial fibrillation protection.